A massively spectacular view of the chemical lives of microbes.
A massively spectacular view of the chemical lives of microbes.
复制标题
微生物化学生命的壮观景象。
DOI：
10.1073/pnas.1207725109
复制
发表时间：
2012
影响因子：
11.1
通讯作者：
Kolter,Roberto
中科院分区：
文献类型：
--
作者：
Traxler,MatthewF;Kolter,Roberto
微生物引领着迷人的化学生命的知识与微生物学本身一样古老。19世纪后期，burton - sanderson(1)的观察结果，经过Pasteur和Joubert(2)的阐述，产生了这样一种观点，即某些微生物分泌的化合物可能对其他微生物的生命产生显著影响。在20世纪早期，这类知识的积累一直稳定地持续着，直到弗莱明开创性地发现青霉素后才出现了巨大的飞跃(3)。钱恩和弗洛里随后将青霉素开发为治疗剂，不仅开创了抗生素的黄金时代，而且开创了整个以小分子天然产物为基础的制药业。从那时起，研究微生物的化学生命主要是通过一次处理一个分子的劳动密集型和耗时的方法。尽管这种历史悠久的方法产生了许多新知识，但近几十年来，发现的速度显著放缓。也许关于小分子天然产物的所有有待发现的东西都已经被发现了。基因组学的出现让这种想法戛然而止；基因组揭示了大量潜在的微生物分泌产物有待发现(4)。然而，实现这一潜力的进展一直很缓慢。在PNAS上，Watrous等人提供了一种全新的方式来观察分泌的微生物产物，这对理解微生物化学生态学的迷人世界提供了巨大的希望(6)。新方法应用快速和高灵敏度的质谱直接鉴定和表征细菌菌落分泌的分子(6)，从而规避了传统质谱方法的许多缺点（最近在参考文献7中进行了综述）。理论上，这种方法可以应用于任何有微生物、非生物或生物定植的可接近表面。有一天，生活在动植物表面的微生物群落可能会用这种方法进行查询，为我们提供迄今为止难以想象的微生物化学丰富性的观点（图1A）。Watrous等人(6)将纳米喷雾解吸电喷雾电离（nano-DESI）质谱和光谱网络构建这两项方法学进展整合到这个令人兴奋的代谢组学分析和天然产物发现的新平台中。在nanoDESI工作流程中（图1B），溶剂通过主毛细管直接泵送到样品表面，在那里感兴趣的分子被解吸。一端靠近表面的次级毛细管抽取样品分析物，随后将其电喷涂到质谱仪入口。这种设置提供了几个引人注目的优点。在两个毛细管之间的大约微升大小的溶剂桥允许以相对高的分辨率直接采样。当被分析物被吸入质谱仪时，样品中成百上千种不同的离子被破碎，它们的
Knowledge that microbes lead fas-cinating chemical lives is as old as microbiology itself. Observations in the late 19th century by Burdon-Sanderson (1) that were elaborated on by Pasteur and Joubert (2) gave rise to the idea that compounds secreted by some microbes could have remarkable effects on the lives of others. The accretion of such knowledge continued steadily through the early years of the 20th century until the quantum leap emanating from Fleming’s seminal discovery of penicillin (3). Chain and Florey’s subsequent development of penicillin as a therapeutic agent ushered in not only the golden era of antibiotics but an entire pharmaceutical industry based largely on small-molecule natural products. Since those days, the chemical lives of microbes have been studied largely through labor-intensive and time-consuming approaches that addressed one molecule at a time. Although this time-honored approach has yielded much new knowledge, the rate of discovery slowed down dramatically in recent decades. Perhaps all there was to discover about small-molecule natural products had been discovered. The advent of genomics put a halt to that idea; genomes revealed a great potential diversity of secreted microbial products waiting to be found (4). However, progress in realizing that potential has been slow (5). In PNAS, Watrous et al. offer a brand new way of viewing secreted microbial products that holds great promise in providing the next quantum leap in understanding the fascinating world of microbial chemical ecology (6). The new approach applies rapid and highly sensitive MS to directly identify and characterize molecules secreted by bacterial colonies (6), thus circumventing many shortcomings of conventional MS approaches (reviewed recently in ref. 7). In theory, this approach could be applied to any accessible surface colonized by microbes, abiotic or biotic. The microbial communities living on the surfaces of plants and animals might some day be queried with this methodology, providing us with heretofore unimaginable views of the richness of microbial chemistry (Fig. 1A). Watrous et al.(6) integrate two methodological advances, namely nanospray desorption electrospray ionization (nano-DESI) MS and spectral network construction, into this exciting new platform for metabolomic profiling and natural products discovery. In the nanoDESI workflow (Fig. 1B), solvent is pumped through a primary capillary directly onto the sample surface, where molecules of interest are desorbed. A secondary capillary with one end positioned near the surface draws up the sample analyte, which is subsequently electrosprayed into the mass spectrometer inlet. This setup offers several compelling advantages. The approximately microliter-sized solvent bridge between the two capillaries allows for direct sampling with relatively high resolution. When the analyte has been aspirated into the mass spectrometer, the hundreds or thousands of different ions from the sample are fragmented, and their